Biological insights from 108 schizophrenia-associated genetic loci.

Nature
Authors
Keywords
Abstract

Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.

Year of Publication
2014
Journal
Nature
Volume
511
Issue
7510
Pages
421-7
Date Published
2014 Jul 24
ISSN
1476-4687
DOI
10.1038/nature13595
PubMed ID
25056061
PubMed Central ID
PMC4112379
Links
Grant list
G0601635 / Medical Research Council / United Kingdom
G0800509 / Medical Research Council / United Kingdom
G0801418 / Medical Research Council / United Kingdom
G0901310 / Medical Research Council / United Kingdom
G1000718 / Medical Research Council / United Kingdom
G1100583 / Medical Research Council / United Kingdom
I01 BX001356 / BX / BLRD VA / United States
I01 BX002395 / BX / BLRD VA / United States
K99 MH101367 / MH / NIMH NIH HHS / United States
MR/L010305/1 / Medical Research Council / United Kingdom
PDA/02/06/016 / Department of Health / United Kingdom
R01 MH040799 / MH / NIMH NIH HHS / United States
R01 MH100141 / MH / NIMH NIH HHS / United States
T32 MH020030 / MH / NIMH NIH HHS / United States
U01 MH094421 / MH / NIMH NIH HHS / United States
U01 MH094421 / MH / NIMH NIH HHS / United States
U01 MH094432 / MH / NIMH NIH HHS / United States
U01 MH096296 / MH / NIMH NIH HHS / United States